EphB2 and EphA4 receptors regulate formation of the principal inter-hemispheric tracts of the mammalian forebrain

S.K.Y. Ho, N. Kovačević, R.M. Henkelman, A. Boyd, T. Pawson and J.T. Henderson (2009) EphB2 and EphA4 receptors regulate formation of the principal inter-hemispheric tracts of the mammalian forebrain. Neuroscience, 160 4: 784-795. doi:10.1016/j.neuroscience.2009.03.013


Author S.K.Y. Ho
N. Kovačević
R.M. Henkelman
A. Boyd
T. Pawson
J.T. Henderson
Title EphB2 and EphA4 receptors regulate formation of the principal inter-hemispheric tracts of the mammalian forebrain
Formatted title
EphB2 and EphA4 receptors regulate formation of the principal inter-hemispheric tracts of the mammalian forebrain
Journal name Neuroscience   Check publisher's open access policy
ISSN 0306-4522
Publication date 2009-06-02
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.neuroscience.2009.03.013
Volume 160
Issue 4
Start page 784
End page 795
Total pages 12
Editor Dr. O P Ottersen
Place of publication United Kingdom
Publisher Pergamon
Collection year 2010
Language eng
Subject C1
9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
1103 Clinical Sciences
Abstract Abstract Previously, we have demonstrated that EphB2 activity is required for proper development of the posterior branch of the anterior commissure (ACpp) within the mammalian forebrain. In the present study, using magnetic resonance imaging (MRI), immunohistochemistry, and in vivo stereotactic fluorescence tracing of EphB2, B3, A4 and combinatorial Eph receptor mutants, we have developed a detailed three-dimensional model of how EphB-class receptors interact to regulate commissural formation within the forebrain. The results demonstrate that EphB2 and EphA4 each regulate distinct aspects of axon guidance within the ACpp. Specifically, while EphB2 is required to retard ACpp axons from projecting aberrantly into the ventral forebrain, EphA4 is required to restrict axons from entering the anterior branch of the anterior commissure (ACpa). Together, EphB2 and EphA4 act synergistically to prevent a subpopulation of axons within the anterior branch of the AC from mis-projecting caudally. Analysis of EphA4 null mice using high resolution MRI reveals for the first time that, in addition to errors in midline guidance, loss of EphA4 results in aberrant lateral and ventral displacement of the ACpa tract. In addition, tracing studies in α-chimerin null mice reveal that EphA4-mediated effects are not regulated through this pathway. Taken together, the results demonstrate that each of the principal guidance decisions within both anterior and posterior tracts of the anterior commissure can be accounted for by the individual and combinatorial actions of EphB2/A4 receptors.
Formatted abstract
Abstract
Previously, we have demonstrated that EphB2 activity is required for proper development of the posterior branch of the anterior commissure (ACpp) within the mammalian forebrain. In the present study, using magnetic resonance imaging (MRI), immunohistochemistry, and in vivo stereotactic fluorescence tracing of EphB2, B3, A4 and combinatorial Eph receptor mutants, we have developed a detailed three-dimensional model of how EphB-class receptors interact to regulate commissural formation within the forebrain. The results demonstrate that EphB2 and EphA4 each regulate distinct aspects of axon guidance within the ACpp. Specifically, while EphB2 is required to retard ACpp axons from projecting aberrantly into the ventral forebrain, EphA4 is required to restrict axons from entering the anterior branch of the anterior commissure (ACpa). Together, EphB2 and EphA4 act synergistically to prevent a subpopulation of axons within the anterior branch of the AC from mis-projecting caudally. Analysis of EphA4 null mice using high resolution MRI reveals for the first time that, in addition to errors in midline guidance, loss of EphA4 results in aberrant lateral and ventral displacement of the ACpa tract. In addition, tracing studies in α-chimerin null mice reveal that EphA4-mediated effects are not regulated through this pathway. Taken together, the results demonstrate that each of the principal guidance decisions within both anterior and posterior tracts of the anterior commissure can be accounted for by the individual and combinatorial actions of EphB2/A4 receptors.

Keyword anterior commissure
MRI
Eph
axon guidance
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 29 Mar 2010, 14:59:22 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital